Context: Cold-water immersion is the criterion standard for
treatment of exertional heat illness. Cryotherapy and water immersion
also have been explored as ergogenic or recovery aids. The kinetics of
inflammatory markers, such as interleukin-6 (IL-6), during cold-water
immersion have not been characterized.

Objective: To characterize serum IL-6 responses to water immersion
at 2 temperatures and, therefore, to initiate further research into the
multidimensional benefits of immersion and the evidence-based selection
of specific, optimal immersion conditions by athletic trainers.

Results: Whole-body cooling rates were greater in the cold
water-bath condition for the first 6 minutes of water immersion, but
during the 90-minute, postexercise recovery, participants in the warm
and cold water-bath conditions experienced similar overall whole-body
cooling. Heart rate responses were similar for both groups. Participants
in the cold water-bath condition experienced an overall slight increase
(30.54% [+ or -] 77.37%) in IL-6 concentration, and participants in the
warm water-bath condition experienced an overall decrease (-69.76% [+ or
-] 15.23%).

Conclusions: We have provided seed evidence that cold-water
immersion is related to subtle IL-6 increases from postexercise values
and that warmer water-bath temperatures might dampen this increase.
Further research will elucidate any anti-inflammatory benefit associated
with water-immersion treatment and possible multidimensional uses of
cooling therapies.

Exercise heat stress has been associated with muscle cell damage,
(1,2) mild endotoxemia, (3,4) and increased risk for exertional heat
illness. (5) The compound stress of physical activity in hot and humid
environments is known to instigate inflammation, (6-8) which might be
implicated in heat-stroke pathophysiology. (9,10) The inflammatory
response to exercise involves acute-phase protein and cytokine
responses, both of which are independent of infection-triggered activity
in the immune system.(11-13 Cytokines are of particular interest due to
their roles in the balance of immune responses between beneficial and
harmful physiologic effects. (14,15) In particular, interleukin-6 (IL-6)
has proinflammatory and anti-inflammatory properties, so it is relevant
to exercise physiology due to the observed relationship with muscle
regeneration and recovery. (16,17) In addition, IL-6 responds to many
different modes, durations, and intensities of exercise or training and
to endogenous and environmental stressors. (13) It increases measurably
with exercise and heat stress and might be a valuable marker of stress
and possibly of recovery.

Recovery from exertional heat illness is best ensured with
cold-water immersion, which is the fastest way to reduce hyperthermic
core temperature. (5,18) Proulx et al (19) identified maximal cooling of
hyperthermic participants when water baths at 2[degrees]C were compared
with 8[degrees]C, 14[degrees]C, and 20[degrees]C. They found no
differences in cooling rates among the 8[degrees]C, 14[degrees]C, and
20[degrees]C water baths, but cooling was effective in all cases. The
relationship between cooling and immune function, or IL-6 specifically,
was first studied by Brenner et al. (20) They demonstrated that exposure
to cold without previous exercise leads to circulating IL-6 increases.
Peake et al (21) measured serum IL-6 concentrations before and after
exercise and during recovery; during the recovery period, participants
rested for 20 minutes after 90 minutes of cycling exercise in warm
(32[degrees]C) environments and were immersed in cold water
(14[degrees]C) for 15 to 20 minutes. The researchers found decreases
that were not different in serum IL-6 concentrations due to water
immersion.

Water immersion is undoubtedly the criterion standard in treating
hyperthermia in exertional heat illness (18) and might have other
recovery or performance benefits. (21-28) Researchers have explored the
possibility that cold-water immersion or cryotherapy might have
beneficial effects in addition to rapid conductive cooling in
hyperthermic athletes and patients (25,29-36); some of these benefits
might be related to cold-induced or cooling-related regulation of
inflammation after intense exercise and heat stress. (21,23,28) Few
researchers have systematically and clearly defined immune-response
kinetics during cold-water immersion after exercise heat stress.

Our research aim was to provide a first-time kinetic analysis of
IL-6, which is a cytokine that clearly is increased with exercise heat
stress, during cold-water immersion. We sought to evaluate IL-6
responses during commonly used cold temperature (11.70[degrees]C [+ or
-] 2.02[degrees]C) water baths (COLD) (21,23,24,26,27,29,37,38) and
during a more easily generated warm, or room, temperature
(23.50[degrees]C [+ or -] 1.00[degrees]C) water bath (WARM), which might
be more applicable or feasible in certain field or clinical settings.

Although we expected the 2 bath conditions to have similar cooling
rates, (19) we hypothesized that subtle molecular differences might
support the multidimensional benefit of one versus the other. Therefore,
our purpose was to provide novel information about serum IL-6 changes
during water immersion with 2 different but comparably effective cooling
temperatures. Our pilot data support future research into the possible
mechanisms by which water immersion might be diversely beneficial. This
future research will support mechanistic, evidence-based prescription of
cold-water immersion, cryotherapies, and other cooling strategies.

METHODS

Participants

We recruited male participants in mid-April from the University of
Connecticut. Nine college-aged men participated in this study. However,
only 8 participants (age = 22 [+ or -] 3 years, height = 1.76 [+ or -]
0.08 m, mass = 77.14 [+ or -] 9.77 kg, body fat = 10% [+ or -] 3%,
maximal oxygen consumption = 50.48 [+ or -] 4.75 mL x [kg.sup.-1] x
[min.sup.-1]) were included in the analysis because 1 participant did
not experience core temperature elevations during exercise heat stress
and required no cold-water immersion therapy. This was not related to
study design but likely due to an exceptional resilience of this
participant's thermoregulatory capabilities. Female volunteers were
not recruited to avoid possible confounding factors from diverse hormone
therapy, contraceptive use, and menstrual cycles; no one has determined
whether these variables might affect IL-6 via endocrine signaling
(35,39) and, if they do, how they affect it. Each potential participant
completed a medical history questionnaire form, and volunteers were
excluded if they indicated use of tobacco; use of medication or dietary
supplements; recent exposure or acclimatization to heat; history of
cardiovascular, metabolic, or respiratory disease; or history of
exertional heat stroke or heat intolerance. All participants provided
written, informed consent, and the University of Connecticut
Institutional Review Board for Human Studies approved the study.

Design

Each participant underwent a familiarization day consisting of
body-composition testing via skinfold measurements, maximal oxygen
consumption measurement, and instruction in the exercise heat protocol.
After this preliminary visit, they took part in a 1-day trial.
Initiation of the exercise-immersion protocol was standardized to
afternoon for all participants. They were randomized into either the
COLD (11.70[degrees]C [+ or -] 2.02[degrees]C) or WARM (23.50[degrees]C
[+ or -] 1.00[degrees]C) immersion group. For analysis and presentation
of data, COLD group participants were numbered 1 through 4, and WARM
group participants were numbered 5 through 8.

During the exercise heat and water-immersion protocols, blood
samples were collected at the immediate postexercise time point: 5
minutes postexercise, when participants entered the water-immersion
tubs; 10 minutes postexercise; 60 minutes postexercise; and 90 minutes
postexercise. The final 2 blood samples were collected during a sitting
equilibration because all 8 participants cooled to 38[degrees]C (core
temperature) within the first 30 minutes; after their core temperatures
reached 38[degrees]C, participants exited the immersion tub and sat for
the remainder of the 90 minutes postexercise.

For further standardization of data results, all participants drank
500 mL of water the evening before testing and 500 mL on the morning of
testing to ensure euhydration. Participants submitted activity logs
(mode, duration, intensity) and diet record, following detailed written
and oral instructions in recording procedures. Data were collected in 2
randomized iterations 10 days apart in late April and early May at the
Human Performance Laboratory of the University of Connecticut. The mean
daily temperatures in Storrs during this time were 9[degrees]C (range,
5[degrees]C-17[degrees]C) and 11[degrees]C (range,
6[degrees]C-17[degrees]C), respectively.

Testing Day Protocols

Familiarization Session. On arrival, participants were instructed
to void their bladders before being weighed in shorts on an electronic
scale (model 349KL; Healthometer Inc, Bridgeview, IL) to the nearest 50
g. We used calipers (Lange skinfold calipers; Cambridge Scientific
Industries, Watertown, MA) to measure skinfold thickness at 7 sites on
the right side of the body. Measurements were made in duplicate and
included chest, triceps, subscapular, suprailiac, umbilical,
midaxillary, and thigh sites. The Jackson and Pollock (40) equation was
used to determine body density, and the Siri equation (36) was used to
calculate percentage of body fat. The maximal oxygen consumption test
was performed using a motorized treadmill protocol in an environmental
chamber (model 2000; Minus-Eleven, Inc, Malden, MA) at 22[degrees]C.
Treadmill (Precor, Woodinville, WA) speed and grade started at 1.52 m/s
(3.4 miles per hour) and 5%, respectively. After 3 minutes, the speed
was increased to 1.78 m/s (4 miles per hour), and the grade was
increased by 2% every 2 minutes until participants reached volitional
cessation. Oxygen consumption was measured breath by breath (30-second
averages) using on-line, open-circuit spirometry (model CPX-D; Medical
Graphics, Inc, St Paul, MN) that was calibrated according to the
manufacturer's guidelines before each test.

Morning Session. Morning protocols were scheduled to begin between
6:30 and 8:00 AM and were staggered to facilitate blood collection and
processing. Upon arrival, participants urinated into a clean, inert,
plastic container; urine was analyzed directly for specific gravity to
verify euhydration ([less than or equal to] 1.020). Wearing only
underwear, participants then were weighed on an electronic scale ([+ or
-] 50 g). They returned later in the day for the exercise and immersion
protocols.

Exercise Protocol. Upon return, participants cycled for
approximately 20 minutes on a cycle ergometer (model 818E; Monark
Ergomedic, Stockholm, Sweden) in the laboratory (temperature =
25[degrees]C [+ or -] 1[degrees]C, relative humidity = 45% [+ or -] 6%)
at a workload equal to 1.5 W/kg body mass. End time was taken as the
onset of sweating by visual and the participant's oral
verification. Next, they consumed a standard meal consisting of a bagel,
cream cheese, a banana, and 200 mL of water; this provided 312 kcal from
carbohydrate, 126 kcal from fat, and 56 kcal from protein. We inserted a
cannula (Critikon, Inc, Tampa, FL) into a superficial forearm vein, and
participants entered the environmental chamber.

Participants stood quietly for 15 minutes inside the chamber to
allow body fluids, plasma volume, and skin temperatures to stabilize.
The environmental conditions in the chamber included a temperature of
37[degrees]C [+ or -] 1[degrees]C and relative humidity of 52% [+ or -]
11%. Exercise was performed on a motorized treadmill at each
participant's fastest walking pace (range among participants,
1.69-1.83 m/s [3.8-4.1 miles per hour]), which had been determined
during the familiarization visit, at a 5% grade for 90 minutes or until
volitional cessation. All participants completed 90 minutes of exercise
and none required emergency interruptions. During exercise heat
exposure, heart rate and rectal temperature were monitored every 15
minutes via telemetry (CorTemp; HQ Inc, Palmetto, FL) and a rectal
thermistor (model YSI 401 rectal probe; Yellow Springs, Yellow Springs,
OH), respectively. The rectal thermistor was inserted 10 cm beyond the
external anal sphincter by the participant before entrance into the
environmental chamber. Before and after heat exposure, participants were
weighed on an electronic scale ([+ or -] 50 g). During exercise,
participants consumed 0.17% body mass of water every 15 minutes.
Treadmill belt speed was verified during each use with a handheld
digital tachometer (model 92-4059-20; Fisher Scientific, Pittsburgh,
PA).

Water Immersion Protocol. Immediately after exercise, time of
exercise was recorded, and a blood sample was collected while the
participant stood, assisted if needed, on the stopped treadmill belt.
Participants were escorted to a nearby locker room where 2 plastic tubs
full of water at either 11.70[degrees]C [+ or -] 2.02[degrees]C or
23.50[degrees]C [+ or -] 1.00[degrees]C had been prepared approximately
30 minutes earlier. Water temperature was measured with a fully
submerged pool thermometer; to ensure that water temperature did not
change, ice chips were prepared for cooling the water baths, and water
was circulated continuously around participants while immersed. Before
entering the tub, they removed all clothing except shorts and underwear,
then sat in a chair beside the tub for 5 minutes. Participants were
allowed to drink water ad libitum in this time after exercise. At 5
minutes postexercise, a blood sample was collected, and participants
were assisted into the tubs where they sat with the water levels up to
their sternums, legs stretched out and completely immersed, and upper
extremities out of the water and resting on the sides of the tubs. Heart
rate and rectal temperature were recorded every minute during immersion.

Participants were immersed only until core temperature had
decreased to 38.0[degrees]C to prevent overshoot and possible mild
hypothermia. When reaching 38.0[degrees]C, participants left the water
and were allowed to towel off and change before being escorted to a
nearby room (temperature = 25[degrees]C [+ or -] 1[degrees]C, relative
humidity = 45% [+ or -] 6%) where they sat quietly in recliners before
the 60-minute and 90-minute postexercise blood draws, thermal sensation
reports, and heart rate measurements. At the final blood draw, we
removed the cannula and ensured the well-being and safety of the
participants before allowing them to depart the laboratory.

Blood Collection

All participants had a flexible, indwelling, 18-gauge Teflon
cannula placed in a superficial forearm vein. A 15.2-cm extension tube
fitted with a 3-way stopcock was attached to the cannula. Patency was
maintained with saline; the tubing (2 mL of dead space) was flushed with
4 mL of blood before each sample was obtained. Each draw was 5 mL into a
dry syringe, which was transferred into a chilled 5-mL endotoxin- and
pyrogen-free blood-collection tube (BD Vacutainer; BD, Franklin Lakes,
NJ). Blood was allowed to clot and immediately processed to ensure
accurate measurement of interleukin. Samples were centrifuged at 3000
rpm for 20 minutes at 4[degrees]C before the resulting serum was
transferred to 1.5-L microcentrifuge tubes and stored at -80[degrees]C
for subsequent analysis of IL-6.

Analytical Methods

Diet records were analyzed for energy, macronutrient content,
sodium content, potassium content, and fluid volume (Nutritionist Pro,
version 1.3; First Databank, Inc, The Hearst Corporation, San Bruno,
CA). Serum was analyzed for IL-6 concentration by enzyme immunoassay
(IL-6 Ultrasensitive Human EIA; Alpco Diagnostics, American Laboratory
Products Co, Windham, NH). The interassay and intra-assay coefficients
of variation (CVs) were 11.1% and 3.0%, respectively. The theoretical
sensitivity of the ultrasensitive IL-6 assay was 0.16 to 10.0 pg/mL.
Interassay CVs were calculated from the average CV of each duplicate
pair. The intra-assay CVs are the mean of the CV of the standards used
to generate the standard curve. Absorbance was read on a multilabel
counter (VersaMax; Molecular Devices, Sunnyville, CA).

[FIGURE 1 OMITTED]

Statistical Analysis

The means [+ or -] standard deviations (SDs) are presented
throughout the "Results" section, but for (nonnormal) IL-6
data, medians and interquartile range are presented as indicated. Fewer
than 4% of the total (120 data points, 40 time points in triplicate)
data points were outside the enzyme-linked immunosorbent assay
sensitivity range and were ascribed to be the mean IL-6 concentrations
of the group (cool-water or warm-water temperature) at the designated
time point. The IL-6 data were not normally distributed but displayed
equal variance between COLD and WARM. The IL-6 at time points 5, 10, 60,
and 90 minutes postexercise and percentage changes from time 0 were
analyzed with nonparametric Kruskal-Wallis tests to calculate
differences across water-temperature treatments. Spearman p correlation
analysis was performed to determine the relationship between IL-6 and
core temperature. Comparison of means on all other normally distributed
variables was performed using a univariate analysis of variance. We used
SPSS (version 14.0, release 2005; SPSS Inc, Chicago, IL) to analyze the
statistics. Significance was established as P [less than or equal to]
.05.

RESULTS

Baseline Measures

All nutritional, hydration, and anthropometric variables between
the COLD and WARM groups were similar. Daily caloric, macronutrient,
sodium, and potassium intake were not different across days and
participants, whereas water intake was greater on the testing day than
the preacclimation day ([F.sub.9,63] = 4.852, P [less than or equal to]
.001, [[eta].sup.2] = 0.409, observed power = 0.998). Urine specific
gravity on familiarization and testing days indicated that all
participants were euhydrated on both days (1.020 [+ or -] 0.005).

The COLD and WARM groups experienced similar heart rate changes
during immersion and recovery. Thus, the WARM and COLD immersion baths
did not result in different cardiovascular responses. Heart rates in
beats per minute are given in Figure 1. We found no differences between
the COLD and WARM groups at each time point ([F.sub.1,78] = 2.037, P
> .05). After entering the baths, both COLD and WARM groups
experienced decreases in heart rate within the first 2 minutes (P <
.05). This heart rate recovery continued through the 90-minute recovery
period postexercise for both groups (P < .001).

Core Temperature

Absolute rectal temperatures were not different between the COLD
and WARM groups. Relative change from the immediate postexercise
temperatures, which were not different, indicated greater cooling for
the COLD than WARM group in the first 6 minutes of immersion. Rectal
temperatures for the COLD and WARM groups are depicted in Figure 2A and
2B. Postexercise rectal temperatures were 39.80[degrees]C [+ or -]
0.23[degrees]C and 39.26[degrees]C [+ or -] 0.61[degrees]C for COLD and
WARM, respectively, and were not different from each other ([F.sub.1,12]
= 2.702, P = .15, [[eta].sup.2] = 0.310, observed power = 0.284). By the
time participants entered the water baths 5 minutes later, rectal
temperature had decreased to 39.75[degrees]C [+ or -] 0.22[degrees]C in
the COLD group and 39.21[degrees]C [+ or -] 0.63[degrees]C in the WARM
group ([F.sub.1,12] = 2.128, P = .20, [[eta].sup.2] = 0.262, observed
power = 0.234). We found no differences between COLD and WARM at each
time point during cooling (P > .05).

Relative changes from immediate postexercise, within COLD and
within WARM, indicated that differences existed in cooling in the first
6 minutes of immersion. Rectal temperature in the COLD group was lower 5
minutes into immersion (time point: 10 minutes) than immediately
postexercise ([F.sub.1,12] = 4.811, P = .049, [[eta].sup.2] = 0.286,
observed power = 0.523). The WARM group did not exhibit rectal
temperatures that were different from their immediate postexercise
temperatures until 60 minutes postexercise. The COLD and WARM groups
experienced different cooling rates for the first 6 minutes of immersion
(Figure 2D).

The total cooling rate from entry into the immersion tub until 90
minutes postexercise for the COLD group (0.62[degrees]C/ min [+ or -]
0.61[degrees]C/min) was more than twice that of the WARM group
(0.25[degrees]C/min [+ or -] 0.59[degrees]C/min), but this difference
was not statistically significant ([F.sub.1,12] = 3.77, P = .08,
[[eta].sub.2] = 0.309, observed power = 0.282). Similarly, the average
immersion time was not different between the WARM (10 [+ or -] 5.48
minutes) and COLD (8 [+ or -] 6.68 minutes) groups.

Interleukin-6

Relative changes from postexercise values were different between
the COLD and WARM groups. The COLD group experienced an increase in
IL-6, whereas the WARM group experienced a decrease in IL-6.
Postexercise IL-6 values were not different between the WARM (5.24 [+ or
-] 6.48 pg/mL; median [+ or -] interquartile range) and COLD (0.93 [+ or
-] 1.78 pg/ mL) groups based on a nonparametric Kruskal-Wallis test (N =
8, [[chi square].sub.1] = 3.000, P = .08). Absolute values for the IL-6
concentrations of both groups are shown in the Table.

Because a measurable qualitative difference existed between
postexercise IL-6 for the COLD and WARM groups, absolute IL-6
concentrations and subsequent changes might not be accurately reflective
of the standardized WARM and COLD effects (Figure 3A). Thus, we used the
percentage change in IL-6 from baseline as a measure of IL-6 change
(Figure 3B). We found no differences in percentage change in IL-6
between the COLD and WARM groups until 90 minutes postexercise. By 90
minutes postexercise, IL-6 in the COLD group had increased by 30.54%,
and IL-6 in the WARM group had decreased slightly by 69.76% (N = 8,
[[chi square].sub.1] = 4.083, P = .04) (Figure 3C). Using within-group
comparisons, we verified that absolute IL-6 concentrations in both
groups were different at 60 minutes and 90 minutes from concentrations
at postexercise (P < .05), supporting the percentage change data.

To explore the possibility that serum IL-6 might be related to core
temperature at a given time point, we analyzed the relationship between
serum IL-6 and core temperature during the COLD and WARM conditions. In
the COLD condition, serum IL-6 remained fairly constant in relationship
to core temperature (P = .40, [rho] = -0.202) (Figure 3B). In the WARM
condition, serum IL-6 seemed to decrease with core temperature (P =
.044, [rho] = 0.454). The IL-6 was not correlated with core temperature
when pooling WARM and COLD condition data (P = .28, [rho] = 0.176). The
2 groups differed by only 2 minutes in cooling time and reached the same
cooling endpoint of 38[degrees]C core temperature.

DISCUSSION

We performed a pilot investigation to provide novel information
about serum IL-6 kinetics after exercise heat stress during water
immersion and recovery. We observed modest changes in IL-6 for both the
COLD and WARM conditions. However, we also observed that the COLD
condition was uniquely associated with percentage increases in serum
IL-6 during postexercise cooling. This finding was in the context of
similar cardiovascular (heart rate) and core temperature recovery during
the 90 minutes postexercise. Given the initial, brief difference in
cooling rate between the COLD and WARM conditions and the brevity
(range, 8-10 minutes) of the cooling time relative to total recovery
time (90 minutes), we conclude that this result requires further
research. Overall, we found that IL-6 might be one marker of subtle
differences between water temperatures that otherwise affect physiology
in similar ways. Further research will highlight mechanisms by which
specific immersion conditions provide benefits related to inflammation
in addition to general whole-body cooling. This type of research will
allow athletic trainers to make decisions with the multidimensional
aspects of recovery in mind.

The efficacy of the COLD and WARM conditions was comparable, but we
noted a difference in cooling rate in the first 6 minutes of water
immersion. Postexercise core temperature was not different between the
COLD and WARM conditions. Rectal temperature continued to decrease to
resting temperatures during the 90-minute recovery. Time to cool was not
different between groups. However, despite a small sample size and only
a 10[degrees]C difference in water-bath temperatures, we found an
initial difference in cooling rates in the first 6 minutes of immersion.
This early difference in cooling rates could have affected lagging
changes in serum IL-6 concentrations, but further research is required.
In the future, researchers also will clarify whether slight differences
like this in cooling relate to notable differences in physiologic or
immune-related benefits. Athletic trainers then will be able to
rationalize certain immersion conditions as more standard, broadly
beneficial prescriptions for recovery or treatment.

When hyperthermic individuals were immersed in water baths
immediately after exercise heat stress, serum IL-6 concentrations did
not change acutely. However, 90 minutes into recovery, once core
temperature was restored to normal, serum IL-6 appeared to increase
slightly (from postexercise values) with colder bath temperatures in
comparison with warmer temperatures (+10[degrees]C). We observed
slightly different, albeit statistically nonsignificant, postexercise
serum IL-6 values for our 2 treatment groups. In considering this, we
present results that represent relative percentage changes in serum IL-6
from postexercise levels. Larger sample sizes in future studies might
eliminate such random variation between experimental groups.
Nevertheless, despite our small sample sizes and the smaller starting
value of the COLD condition, the COLD group experienced an increase of
approximately 31% by 90 minutes of recovery. During the 90 minutes,
serum IL-6 concentrations consistently increased in the COLD condition
but decreased slightly or reached a plateau in the WARM condition
(Figure 3C). Putting our pilot findings in the context of a few other
studies in which researchers have provided evidence that cold-water
immersion or cold exposure might affect key inflammatory cytokines
highlights the possibility that specific immersion conditions not only
might promote cooling but also might benefit athletes and patients in
other ways.

For example, Brenner et al (20) observed increased plasma IL-6
concentrations after 1 hour of exposure to cold air in resting
participants and after 2 hours when the exposure to cold was preceded by
exercise with a thermal clamp or passive heating. Without previous
exercise or heat stress, cold exposure induced an increase in plasma
IL-6 of approximately 53% after 1 hour and of approximately 85% by 2
hours of exposure to cold air. Adding exercise with a thermal clamp or
having participants exercise in water that prevented increases in core
temperature resulted in an increase in IL-6 of approximately 50% after 1
hour of exposure to cold and of approximately 75% after 2 hours. From
these qualitative observations, exercise alone did not seem to
contribute to any changes in IL-6 kinetics during exposure to cold.

In their passive-heating group, Brenner et al (20) found that IL-6
increased approximately 30% after 1 hour of exposure to cold and
approximately 113% after 2 hours. From approximate qualitative
observations such as these, increases in core temperature seem to
contribute to perhaps a dampening of increases in IL-6 caused by 1 hour
of exposure to cold. Supporting this speculation is the observation that
combined increases in core temperature with exercise before exposure to
cold resulted in an increase in IL-6 of approximately 45% after 1 hour
of cold exposure and of approximately 60% after 2 hours. We did not
investigate any functional implications of IL-6 responses, so future
research is required to determine whether dampening or exacerbating IL-6
increases is more desirable in treating exercise heat stress. The
decisions regarding water-immersion conditions, because they are based
in inflammatory responses, could affect recovery or other treatments
prescribed simultaneously for an athlete or patient.

Unlike Brenner et al, (20) Peake et al (21) found no effect of
cold-water immersion on circulating IL-6 after exercise heat stress.
They speculated that their results were divergent because they
introduced water immersion 20 minutes after the end of exercise rather
than immediately after exercise. We hypothesize that the effects of
delayed water immersion in the study by Peake et al (21) support the
idea that without rapid cooling, postexercise IL-6 might eventually
return to resting levels, depending on the intensity of exercise heat
stress and degree of hyperthermia experienced. Further research also
will characterize the timing of water immersion and how that affects
inflammation. This information will better arm health care providers
with information to prescribe the best cooling therapy or
recovery/ergogenic treatment in light of all the other factors that have
a basis in inflammatory signaling and regulation.

CONCLUSIONS

Water immersion is the criterion standard for treating hyperthermia
in exertional heat illness, (18) and water immersion, body cooling, and
cryotherapy all seem to have some mechanistic basis in regulating
inflammation. (25,29-34) Coaches, athletic trainers, and clinical
professionals prescribe cold-water immersion for various reasons under
diverse circumstances. Better understanding the effect of immersion
therapy on inflammation will equip professionals with information about
how best to prescribe such therapy in the context of other prophylactic
and treatment modalities, ergogenic aids, and commonly used
antiinflammatory or pharmacologic remedies used in the course of
training, competition, and recovery. Understanding the fundamental
molecular and cellular effects of a therapy, such as water immersion,
also allows health care providers to make informed decisions about the
optimal conditions of a clearly beneficial modality, such as water
immersion.

Key Points

* Changes in interleukin-6 were modest with immersion in cold and
warm water baths.

* The 2 water-bath temperatures had different initial cooling
efficiencies, but over a 90-minute, postexercise recovery, participants
in both groups experienced similar whole-body cooling.

* Interleukin-6 might be a marker of subtle differences between
water temperatures that otherwise affect physiology in similar ways.